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Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

Migliori M, Cantaluppi V, Mannari C, Bertelli AA, Medica D, Quercia AD, Navarro V, Scatena A, Giovannini L, Biancone L, Panichi V - PLoS ONE (2015)

Bottom Line: The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production.In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Nephrology and Dialysis Unit, Versilia Hospital, Lido di Camaiore, Italy.

ABSTRACT

Introduction: Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities.

Aim of the study: The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury.

Results: CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.

Conclusion: The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

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DAF-2 DA detected fluorescence.A) L-Arg stimulated fluorescence emission which peaked at 30 min (*p<0.01 vs controls). L-NAME was utilized as negative control (§p<0.05 vs L-Arg). B) CAF 100 nM and CAF 1 μM enhanced NO dependent fluorescence (*p<0.01 vs controls). CAF 1 μM induced NO release was significantly (#p<0.05) higher in respect to CAF 100 nM. Results are expressed as average±1SD of 6 different experiments.
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pone.0117530.g003: DAF-2 DA detected fluorescence.A) L-Arg stimulated fluorescence emission which peaked at 30 min (*p<0.01 vs controls). L-NAME was utilized as negative control (§p<0.05 vs L-Arg). B) CAF 100 nM and CAF 1 μM enhanced NO dependent fluorescence (*p<0.01 vs controls). CAF 1 μM induced NO release was significantly (#p<0.05) higher in respect to CAF 100 nM. Results are expressed as average±1SD of 6 different experiments.

Mentions: NO baseline production by HUVECs was also evaluated by quantitative fluorescence emission generated by DAF-2 DA oxidation. L-Arg but not L-NAME stimulated fluorescence emission that peaked at 30 min (Fig. 3A). The analysis of fluorescence intensity showed a significant increase in DAF-2 DA oxidation in respect to L-Arg after incubation with CAF 100nM or 1μM (Fig. 3B) in a dose dependent manner. TYR did not affect NO baseline production.


Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

Migliori M, Cantaluppi V, Mannari C, Bertelli AA, Medica D, Quercia AD, Navarro V, Scatena A, Giovannini L, Biancone L, Panichi V - PLoS ONE (2015)

DAF-2 DA detected fluorescence.A) L-Arg stimulated fluorescence emission which peaked at 30 min (*p<0.01 vs controls). L-NAME was utilized as negative control (§p<0.05 vs L-Arg). B) CAF 100 nM and CAF 1 μM enhanced NO dependent fluorescence (*p<0.01 vs controls). CAF 1 μM induced NO release was significantly (#p<0.05) higher in respect to CAF 100 nM. Results are expressed as average±1SD of 6 different experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390339&req=5

pone.0117530.g003: DAF-2 DA detected fluorescence.A) L-Arg stimulated fluorescence emission which peaked at 30 min (*p<0.01 vs controls). L-NAME was utilized as negative control (§p<0.05 vs L-Arg). B) CAF 100 nM and CAF 1 μM enhanced NO dependent fluorescence (*p<0.01 vs controls). CAF 1 μM induced NO release was significantly (#p<0.05) higher in respect to CAF 100 nM. Results are expressed as average±1SD of 6 different experiments.
Mentions: NO baseline production by HUVECs was also evaluated by quantitative fluorescence emission generated by DAF-2 DA oxidation. L-Arg but not L-NAME stimulated fluorescence emission that peaked at 30 min (Fig. 3A). The analysis of fluorescence intensity showed a significant increase in DAF-2 DA oxidation in respect to L-Arg after incubation with CAF 100nM or 1μM (Fig. 3B) in a dose dependent manner. TYR did not affect NO baseline production.

Bottom Line: The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production.In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Nephrology and Dialysis Unit, Versilia Hospital, Lido di Camaiore, Italy.

ABSTRACT

Introduction: Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities.

Aim of the study: The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury.

Results: CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.

Conclusion: The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

Show MeSH
Related in: MedlinePlus